Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice
DC Field | Value | Language |
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dc.contributor.author | Ahmad, Ashfaq | - |
dc.contributor.author | Ali, Tahir | - |
dc.contributor.author | Park, Hyun Young | - |
dc.contributor.author | Badshah, Haroon | - |
dc.contributor.author | Rehman, Shafiq Ur | - |
dc.contributor.author | Kim, Myeong Ok | - |
dc.date.accessioned | 2022-12-26T18:48:25Z | - |
dc.date.available | 2022-12-26T18:48:25Z | - |
dc.date.created | 2022-12-13 | - |
dc.date.issued | 2017-04 | - |
dc.identifier.issn | 0893-7648 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gnu/handle/sw.gnu/13791 | - |
dc.description.abstract | Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (A beta) and the hyperphosphorylation of tau proteins in the brain. The deposition of A beta aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the A beta(1-42) mouse model of AD. Single intracerebroventricular injections of A beta(1-42) (3 mu l/5 min/mouse) markedly induced memory/synaptic deficits, neuroinflammation, and neurodegeneration. Intraperitoneal injections of fisetin at a dose of 20 mg/kg/day for 2 weeks starting 24 h after A beta(1-42) injection significantly decreased the A beta(1-42)-induced accumulation of A beta, BACE-1 expression, and hyperphosphorylation of tau protein at serine 413. Fisetin treatment also markedly reversed A beta(1-42)-induced synaptic dysfunction by increasing the levels of both presynaptic (SYN and SNAP-25) and postsynaptic proteins (PSD-95, SNAP-23, p-GluR1 (Ser 845), p-CREB (Ser 133) and p-CAMKII (Thr 286) and ultimately improved mouse memory, as observed in the Morris water maze test. Fisetin significantly activated p-PI3K, p-Akt (Ser 473), and p-GSK3 beta (Ser 9) expression in A beta(1-42)-treated mice. Moreover, fisetin prevented neuroinflammation by suppressing various activated neuroinflammatory mediators and gliosis; it also suppressed the apoptotic neurodegeneration triggered by A beta(1-42) injections in the mouse hippocampus. Fluorojade-B and immunohistochemical staining for caspase-3 revealed that fisetin prevented neurodegeneration in A beta(1-42)-treated mice. Our results suggest that fisetin has a potent neuroprotective effect against A beta(1-42)-induced neurotoxicity. These results demonstrate that polyphenolic flavonoids such as fisetin could be a beneficial, effective and safe neuroprotective agent for preventing neurological disorders such as AD. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | SPRINGER | - |
dc.subject | INDUCED NEURON DEATH | - |
dc.subject | PROTEIN-KINASE-B | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | TAU HYPERPHOSPHORYLATION | - |
dc.subject | INDUCED NEUROTOXICITY | - |
dc.subject | SYNAPTIC PLASTICITY | - |
dc.subject | IN-VIVO | - |
dc.subject | THERAPEUTIC STRATEGIES | - |
dc.subject | SIGNALING PATHWAY | - |
dc.subject | MOUSE HIPPOCAMPUS | - |
dc.title | Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Myeong Ok | - |
dc.identifier.doi | 10.1007/s12035-016-9795-4 | - |
dc.identifier.scopusid | 2-s2.0-84960079296 | - |
dc.identifier.wosid | 000398506900055 | - |
dc.identifier.bibliographicCitation | MOLECULAR NEUROBIOLOGY, v.54, no.3, pp.2269 - 2285 | - |
dc.relation.isPartOf | MOLECULAR NEUROBIOLOGY | - |
dc.citation.title | MOLECULAR NEUROBIOLOGY | - |
dc.citation.volume | 54 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 2269 | - |
dc.citation.endPage | 2285 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.subject.keywordPlus | INDUCED NEURON DEATH | - |
dc.subject.keywordPlus | PROTEIN-KINASE-B | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | TAU HYPERPHOSPHORYLATION | - |
dc.subject.keywordPlus | INDUCED NEUROTOXICITY | - |
dc.subject.keywordPlus | SYNAPTIC PLASTICITY | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | THERAPEUTIC STRATEGIES | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | MOUSE HIPPOCAMPUS | - |
dc.subject.keywordAuthor | Alzheimer&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | Beta-amyloid (A beta(1-42)) | - |
dc.subject.keywordAuthor | Fisetin | - |
dc.subject.keywordAuthor | Synaptic dysfunctions | - |
dc.subject.keywordAuthor | Neuroinflammation | - |
dc.subject.keywordAuthor | Neurodegeneration | - |
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